Faculty Bibliography

[This corrects the article DOI: 10.1371/journal.pone.0038915.].

Heart failure (HF) is a devastating condition characterized by poor quality of life, numerous complications, high rate of readmission and increased mortality. HF is the most common cause of hospitalization in the United States especially among people over the age of 64 years. The number of people grappling with the ill effects of HF is on the rise as the number of people living to an old age is also on the increase. Several factors have been attributed to these high readmission and mortality rates among which are; poor adherence with therapy, inability to keep up with clinic appointments and even failure to recognize early symptoms of HF deterioration which may be a result of cognitive impairment. Therefore, this review seeks to compile the most recent information about the links between HF and dementia or cognitive impairment. We also assessed the prognostic consequences of cognitive impairment complicating HF, therapeutic strategies among patients with HF and focus on future areas of research that would reduce the prevalence of cognitive impairment, reduce its severity and also ameliorate the effect of cognitive impairment coexisting with HF.

Background We hypothesized that neo-epitope-based prediction using an advanced in silico T cell epitope screening system (AncerTM) may better identify patients with improved prognosis than tumor mutation burden. Analysis of genomic data derived from the muscle-invasive bladder cancer (BLCA) cohort of The Cancer Genome Atlas (TCGA) database for CD4, CD8, and Treg neo-epitopes was performed to determine whether AncerTM would improve prognostic stratification compared to tumor mutational burden (TMB). Methods BLCA patient mutanomes (n=412) were retrieved from the TCGA and evaluated with AncerTM, an innovative and automated neo-epitope screening platform that combines proprietary machine learningbased HLA I and HLA II neo-epitope identification tools with removal of inhibitory regulatory T cell epitopes for neo-epitope ranking and personalized cancer vaccine design. BLCA patients were separated based on median TMB or neo-epitope burdens. We investigated the effect of integrating both CD8 and CD4 neo-epitope burdens as most mutanome pipelines exclusively focus on the identification of Class I neo-epitopes. Overall survival was analyzed using the Kaplan-Meier method and differences analyzed by log-rank testing. Results Compared to low TMB, high TMB was significantly associated with improved survival (p = 0.0001, difference of 38.5 months in median survival, Figure 1). Improved differentiation of median survival times was obtained when separating patients based on their Class I neoepitope content, as estimated by AncerTM (p < 0.0001, difference of 59.8 months in median survival). Adding Class II neo-epitope burden further increased separation of OS times, showcased by a 69.6-month increase in median survival for BLCA patients with both high CD8 and high CD4 neo-epitope contents compared to other patients (p = 0.0001). Since we discovered that Class II neo-epitopes can induce inhibitory responses, we further evaluated whether the screening of these detrimental sequences could improve our analysis. Upon identifying Class II neo-epitopes likely to induce T effector (Teff) responses, we found that the median survival of patients with high CD8 and high CD4 Teff contents was extended by nearly 4 months to 73.4 months compared, to the remainder of the cohort (p < 0.0001, Figure 2). Conclusions Our analysis suggests that optimal host-immune recognition of CD8+, CD4+, and Treg epitopes plays a key role in cancer survival. While defining CD8 neo-epitope burden enhanced associations with OS, the inclusion of CD4 Teff neo-epitope burden substantially helped identify long-term survivors. These results suggest that defining the number of true neo-epitopes using AncerTM may represent a novel prognostic or predictive biomarker

Antithrombotic therapy for stroke prevention in patients with atrial fibrillation (AF) has dramatically shifted from warfarin, a vitamin K antagonist, to the direct oral anticoagulants (DOACs) such as dabigatran, apixaban, and rivaroxaban. In patients with contraindications to oral anticoagulation, left atrial appendage occlusion (LAAO) devices, such as the Watchmanâ„¢ device, may be considered; however, temporary postimplantation antithrombotic therapy is still a recommended practice. We present a case of complex antithrombotic management, post LAAO device implantation, designed to avoid drug interactions with concomitant rifampin use and remained necessary secondary to subsequent device leak. This case highlights the challenges of antithrombotic therapy post LAAO device placement in a complex, but representative, patient.

Background: The growing opioid overdose epidemic has grappled the nation with the CDC now reporting that drug overdose deaths have become the most common cause of death for young people. Medical education has historically ignored substance use disorders, and though they generally require all medical students to learn basic life support, they have not taught how to respond to opioid overdoses. Further, medical education is moving towards modalities which utilize adult learning theory. One such modality are online modules. However, there are few studies comparing their outcomes with traditional lectures. Previously, the authors compared in-person and online training of medical students to respond to opioid overdoses using naloxone in a non-randomized controlled setting, which showed no meaningful differences in knowledge, attitudes, and preparedness outcomes for students. In this paper, the authors attempt to use a randomized controlled trial to compare the two educational modalities at a second urban medical school.
Objective(s): The author's primary objective was to demonstrate non-inferiority of online compared to in-person training for knowledge. Our secondary objective were to show non-inferiority of online compared to in-person training attitudes, and preparedness.
Method(s): Our study received IRB exemption as an education intervention. As a part of a transition to clinical clerkships curriculum used for second year medical students, second year medical students in an urban medical school were randomized into training sessions by the office of medical education without foreknowledge of the planned study. Students taking the online training were provided with a link to online modules with pre- and post-tests and video based lectures. Students randomized to the in-person training group took a pre-test just prior to receiving an oral lecture, and then immediately completed a post-test. Paired student's t-tests were used to compare measurements for each group in knowledge, attitudes, and preparedness, and Cohen's D was used to measure the effect size of the change. We calculated 99% confidence intervals for each measure and utilized a margin of non-inferiority of 5%.
Result(s): The in-person group demonstrated a statistically significant increase in knowledge, a non-statistically significant decrease in self-reported preparedness, and a small non-statistically significant increase in attitudes, see Table 1. The online group demonstrated a statistically significant increase in knowledge and self-reported preparedness, without a statistically significant change in attitudes, see Table 1. 99% CIs were [-0.20, 1.09] for knowledge, [6.51, 10.93] for preparedness, and [-2.32, 1.59] for attitudes, see Figure 1.
Conclusion(s): Online training for opioid overdose prevention training provided non-inferior outcomes for knowledge, preparedness, and attitudes. This study supports the use of online opioid overdose prevention training as a non-inferior alternative to in-person training